Effect of phenolic glycolipids from Mycobacterium kansasiion proinflammatory cytokine release. A structure-activity relationship study

The cell wall of pathogenic mycobacteria is abundant with virulence factors, among which phenolic glycolipids (PGLs) are prominent examples. Mycobacterium kansasii, an important opportunistic pathogen, produces seven PGLs and their effect on the release of important proinflammatory cytokines that me...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2015-04, Vol.6 (5), p.3161-3172
Main Authors: Elsaidi, Hassan RH, Lowary, Todd L
Format: Article
Language:English
Subjects:
Cytokines
Methylation
Mycobacterium
Mycobacterium kansasii
Optimization
Pathogens
Progressions
Tuberculosis
Virulence
Walls
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Summary:The cell wall of pathogenic mycobacteria is abundant with virulence factors, among which phenolic glycolipids (PGLs) are prominent examples. Mycobacterium kansasii, an important opportunistic pathogen, produces seven PGLs and their effect on the release of important proinflammatory cytokines that mediate disease progression has not been investigated. We previously showed that proinflammatory cytokines are modulated by PGLs from M. tuberculosis, M. lepraeand M. bovis. In this paper we describe the synthesis of a series of 17 analogs of M. kansasiiPGLs containing a truncated aglycone. Subsequently, the effect of these compounds on the release of proinflammatory cytokines (TNF- alpha , IL-6, IL-1 beta , MCP-1) and nitric oxide (NO) was evaluated. These compounds exerted an immunoinhibitory effect on the release of the tested cytokines. The concentration-dependent inhibitory profile of the tested molecules was also found to be dependent on the methylation pattern of the molecule and was mediated viatoll-like receptor (TLR)-2. This study led to the discovery of a glycolipid (18) that shows promising potent anti-inflammatory properties making it a potential candidate for further optimization of its anti-inflammatory profile.
ISSN:2041-6520
2041-6539
DOI:10.1039/c4sc04004j